Antidepressants improve disease course in inflammatory bowel disease

Copenhagen, Denmark: Antidepressants not only help inflammatory bowel disease (IBD) patients to cope up with psychological comorbidities but was also found beneficial for the disease course among patients with ulcerative colitis (UC) and Crohn’s disease (CD), according to a new study.

The results of the review of nationwide Danish registry, published in the journal Inflammatory Bowel Diseases, showed that the use of antidepressants significantly lowered relapse rate in UC and CD patients.

Marie Skov Kristensen, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark, and colleagues conducted this study to examine the influence of antidepressants on the disease course among patients with UC and CD.

The positive effect on disease activity was especially pronounced in patients with no exposure to antidepressants before IBD onset and held regardless of whether the antidepressants were taken as monotherapy or as part of combination therapy, the authors noted.

Adjusting for various confounders, the results showed a lower incidence of disease activity in antidepressant users versus non-users in both CD and UC patients, with an incidence rate ratio (IRR) of 0.75 for CD (95% confidence interval 0.68-0.82) and 0.90 for UC (95% CI 0.84-0.95).

A total of 42,890 patients were included in the analysis, of whom 29,804 (69.5%) had UC and 13,086 (30.5%) had CD. Women accounted for 52.5% of UC patients and 54.9% of CD patients.

About 5% of patients in both groups had anxiety or depression and about 80% in both groups had started antidepressant therapy before developing IBD, with about 20% having their first antidepressant prescription after developing IBD.

Across the measures of disease activity, antidepressant users in both IBD groups had a significantly lower risk of initiating step-up medication with corticosteroids and anti-tumor necrosis factor (TNF) agents, as well as a lower risk of IBD-related hospitalization. Antidepressants included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and mirtazapine, used either alone or in combination.

Stratified by antidepressant type, the IRRs for disease activity in CD patients with post-IBD antidepressant use only versus no exposure ever were 0.23 for SSRIs, 0.28 for mirtazapine, and 0.60 for mixed use.

In UC, the corresponding IRRs were 023, 0.13, and 0.72, and for mixed use, 0.80.

The investigators also found markedly lower rates of disease activity for both conditions in patients unexposed to antidepressants before IBD onset: IRR for CD 0.51 (95% CI 0.43-0.62); and IRR for UC 0.67 (95% CI 0.59-0.75).

Kristensen and colleagues noted that in terms of potential pathways, antidepressants affect levels of pro-inflammatory cytokines such as interleukin and TNF, known to be involved in the pathogenesis of IBD. "Hence, decreased levels of pro-inflammatory cytokines may explain the observed favorable influence on the course of IBD," the team wrote, adding that antidepressants also positively affect brain-gut interaction.

The team hypothesized that patients treated pre-IBD for psychiatric comorbidity may not see further benefit from the potential anti-inflammatory effect of the drugs when treated after IBD onset. In addition, patients receiving antidepressants pre-IBD may be more vulnerable during the disease course because of psychological challenges unrelated to IBD that increase relapse risk. Despite the high prevalence of anxiety and depression in IBD, however, many patients do not receive appropriate psychiatric treatment," the researchers stated.

"Antidepressants have the potential to be an adjuvant treatment to the conventional therapy for IBD, similar to treatment for irritable bowel syndrome," the authors wrote, adding that the time has come for randomized controlled trials.

Moreover, filled prescriptions may not fully reflect actual intake, and specification of antidepressant doses was not possible. Furthermore, when stratifying analyses by antidepressant subtype, several categories had such small numbers that it was difficult to fully interpret the findings. In addition, the register offered no information on smoking, adherence to medications, or non-pharmacological treatment for presumed depression or anxiety, making it impossible to rule out potential confounding from non-pharmacological treatment, the team said.

In addition, the results may not be generalizable to patients with mild disease activity as the cohort had signs of moderate-to-severe activity. Also, the researchers said, confounding by indication could not be ruled out, and antidepressant users may be different from nonusers according to unmeasured confounding.

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